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自噬诱导剂雷帕霉素与溶瘤腺病毒联合使用可提高对癌细胞的抗肿瘤效果。

Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells.

作者信息

Cheng Pei-Hsin, Lian Serena, Zhao Robin, Rao Xiao-Mei, McMasters Kelly M, Zhou Heshan Sam

机构信息

Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.

出版信息

Virol J. 2013 Sep 23;10:293. doi: 10.1186/1743-422X-10-293.

DOI:10.1186/1743-422X-10-293
PMID:24059864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3850263/
Abstract

BACKGROUND

Combination of oncolytic adenoviruses (Ads) and chemotherapy drugs has shown promising therapeutic results and is considered as a potential approach for cancer therapy. We previously have shown that autophagy may generate decomposed cellular molecules that can be used as nutrition to support virus replication in cancer cells. In this study, we evaluated a unique combination of the novel oncolytic Ad-cycE with rapamycin, an autophagy inducer and first-line chemotherapeutic drug.

METHODS

The combination of oncolytic Ad-cycE and the autophagy inducer rapamycin was assessed for enhanced antitumor effect. We also evaluated the combined effects of rapamycin and Ad-cycE on cancer cell viability. The interaction between Ad-cycE and rapamycin was analyzed with Calcusyn (Biosoft, Ferguson, MO).

RESULTS

We show that rapamycin induces autophagy, enhances Ad E1A expression and increases Ad oncolytic replication. Combination of rapamycin and Ad-cycE elicits stronger cytotoxicity than single treatment alone. The analyzed data indicates that the Ad-cycE and rapamycin combination has a significantly synergistic antitumor effect.

CONCLUSIONS

Our study provides a new insight into vector development and demonstrates the novel roles of autophagy in adenovirus replication. The combination of autophagy-induced chemotherapy and oncolytic virotherapy may be a new approach to improve future cancer treatment.

摘要

背景

溶瘤腺病毒（Ads）与化疗药物联合使用已显示出有前景的治疗效果，被认为是一种潜在的癌症治疗方法。我们之前已经表明，自噬可能产生可作为营养物质用于支持癌细胞中病毒复制的分解细胞分子。在本研究中，我们评估了新型溶瘤腺病毒Ad-cycE与雷帕霉素（一种自噬诱导剂和一线化疗药物）的独特组合。

方法

评估溶瘤腺病毒Ad-cycE与自噬诱导剂雷帕霉素联合使用时增强的抗肿瘤效果。我们还评估了雷帕霉素和Ad-cycE对癌细胞活力的联合作用。使用Calcusyn（Biosoft，密苏里州弗格森）分析Ad-cycE与雷帕霉素之间的相互作用。

结果

我们表明雷帕霉素诱导自噬，增强腺病毒E1A表达并增加腺病毒的溶瘤复制。雷帕霉素与Ad-cycE联合使用比单独单一治疗引发更强的细胞毒性。分析数据表明Ad-cycE与雷帕霉素联合具有显著的协同抗肿瘤作用。

结论

我们的研究为载体开发提供了新的见解，并证明了自噬在腺病毒复制中的新作用。自噬诱导化疗与溶瘤病毒疗法的联合可能是改善未来癌症治疗的一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/5a0c4020bbab/1743-422X-10-293-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/4b1b4d989153/1743-422X-10-293-1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/b9416f589974/1743-422X-10-293-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/532525238331/1743-422X-10-293-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/5a0c4020bbab/1743-422X-10-293-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/4b1b4d989153/1743-422X-10-293-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/ae48b3f0405b/1743-422X-10-293-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/169429274fc1/1743-422X-10-293-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/87528d601629/1743-422X-10-293-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/c49e865f7521/1743-422X-10-293-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/b9416f589974/1743-422X-10-293-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/532525238331/1743-422X-10-293-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13c/3850263/5a0c4020bbab/1743-422X-10-293-8.jpg

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